Anticalculus oral composition

ABSTRACT

An oral composition such as a toothpaste (including gel or cream), mouthwash, lozenge, chewing gum or tooth powder containing a calculus-inhibiting amount of a linear molecularly dehydrated polyphosphate salt and, to inhibit enzymatic hydrolysis of said polyphosphate salt in saliva, a combination of a fluoride ion-providing source and a synthetic linear polymeric polycarboxylate.

This invention relates to oral compositions containing an anticalculusagent.

Calculus is a hard, mineralized formation which forms on the teeth.Regular brushing aids in preventing a rapid buildup of these deposits,but even regular brushing is not sufficient to remove all of thecalculus deposits which adhere to the teeth. Calculus is formed on theteeth when crystals of calcium phosphates begin to be deposited in thepellicle and extracellular matrix of the dental plaque and becomesufficiently closely packed together for the aggregates to becomeresistant to deformation. There is no complete agreement on the route bywhich calcium and orthophosphate ultimately become the crystallinematerial called hydroxyapatite (HAP). It is generally agreed, however,that at higher saturations, that is, above the critical saturationlimit, the precursor to crystalline HAP is an amorphous ormicrocrystalline calcium phosphate. "Amorphous calcium phosphate"although related to hydroxyapatite differs from it in atomic structure,particle morphology, and stoichiometry. The X-ray diffraction pattern ofamorphous calcium phosphate shows broad peaks typical of amorphousmaterials, which lack the long-range atomic order characteristic of allcrystalline materials, including HAP. It is apparent therefore thatagents which effectively interfere with crystalline growth of HAP willbe effective as anticalculus agents. A suggested mechanism by which theanticalculus agents of this invention inhibit calculus formationprobably involves an increase of the activation energy barrier thusinhibiting the transformation of precursor amorphous calcium phosphateto HAP.

Studies have shown that there is a good correlation between the abilityof a compound to prevent HAP crystalline growth in vitro and its abilityto prevent calcification in vivo, provided of course that such compoundis stable in and inert to saliva and its components.

It is well known in the art that water soluble hexametaphosphates,tripolyphosphates and pyrophosphates and the like are effective calciumand magnesium ion suppressors, inhibitors, sequestrants and/or chelatingagents, and are effective inhibitors of HAP formation in vitro. U.S.Pat. No. 4,515,772 issued May 7, 1985 to Parran et al discloses andclaims oral anticalculus compositions containing a fluoride ion sourceand soluble dialkali metal pyrophosphates alone or admixed withtetraalkali metal pyrophosphates. The voluminous number of acknowledgedprior art and "References Cited" in this patent indicate the many usesand functions of these polyphosphates hitherto proposed in oralcompositions.

However, as in part admitted in the aforesaid patent disclosure and asshown hereinafter, these linear molecularly dehydrated polyphosphates(i.e. hexametaphosphates, tripolyphosphates, pyrophosphates, etc.) incommon, when introduced into the oral cavity and/or saliva aresignificantly hydrolyzed by salivary enzymes (phosphatases) toorthophosphates which are ineffective as inhibitors of HAP formation.

It is an object of this invention to provide an improved anticalculusoral composition which will not be subject to one or more of the aboveproblems and disadvantages.

A further object of the invention is to provide an oral compositionwhich inhibits the transformation of amorphous calcium phosphate to HAPcrystal structure normally associated with calculus.

Another object of this invention is the provision of an improved methodfor inhibiting the formation of calculus.

Other objects and advantages will appear as the description proceeds.

In accordance with certain of its aspects, this invention relates to anoral composition containing in an orally acceptable vehicle an effectiveanticalculus amount of one or a mixture of linear molecularly dehydratedpolyphosphate salts as essential anticalculus agent, and as combinationinhibitor against enzymatic hydrolysis of said agent in saliva, anamount of a fluoride ion source sufficient to supply about 25-2,000 ppmof fluoride ions and about 0.05-3% of a synthetic anionic linearpolymeric polycarboxylate having a molecular weight of about 1,000 toabout 1,000,000.

Compounds providing a source of fluoride ion have been profuselydisclosed in the prior art as anti-caries agents but not for inhibitingsalivary hydrolysis of the linear polyphosphate salts employed herein asanticalculus agents. Synthetic anionic linear polymeric polycarboxylatesand their complexes with various cationic germicides, zinc and magnesiumhave been previously disclosed as anticalculus agents per se in, forexample U.S. Pat. No. 3,429,963 to Shedlovsky and instant assignee, U.S.Pat. No. 4,152,420 to Gaffar and instant assignee, U.S. Pat. No.3,956,480 to Dichter et al and instant assignee, U.S. Pat. No. 4,138,477to Gaffar and instant assignee, and U.S. Pat. No. 4,183,914 to Gaffar etal. None of these patents however nor any other known prior art,discloses use of such polycarboxylates alone for inhibiting salivaryhydrolysis of said linear polyphosphates, much less in combination witha compound providing a source of fluoride ion. It is to be understoodthat the synthetic anionic linear polymeric polycarboxylates per sedisclosed in these patents are operative in the compositions and methodsof this invention and such disclosures are to that extent incorporatedherein by reference thereto.

The linear molecularly dehydrated polyphosphate salts operative hereinas anticalculus agents are well known, being generally employed in theform of their wholly or partially neutralized water soluble alkali metal(e.g. potassium and preferably sodium) or ammonium salts, and anymixtures thereof. Representative examples include sodiumhexametaphosphate, sodium tripolyphosphate, disodium diacid, trisodiummonoacid and tetrasodium pyrophosphates and the like. Linearpolyphosphates correspond to (NaPO3)_(n) where n is about 2 to about125. They are generally employed in the instant oral compositions inapproximate weight amounts of 0.1 to 7%, preferably 0.1 to 6%, morepreferably 2 to 6%. When n is at least 3 in (NaPO₃)_(n), saidpolyphosphates are glassy in character.

The synthetic anionic linear polymeric polycarboxylates operative hereinare likewise, as indicated above, well known, being employed in the formof their partially or preferably fully neutralized water soluble alkalimetal (e.g. potassium and preferably sodium) or ammonium salts.Preferred are 1:4 to 4:1 copolymers of maleic anhydride or acid withanother polymerizable ethylenically unsaturated monomer, preferablymethyl vinyl ether (methoxyethylene) having a molecular weight (M.W.) ofabout 30,000 to about 1,000,000. These copolymers are available forexample as Gantrez AN 139 (M.W. 500,000), A.N. 119 (M.W. 250,000) andpreferably S-97 Pharmaceutical Grade (M.W. 70,000), of GAF Corporation.The terms "synthetic" and "linear" are intended to exclude knownthickening or gelling agents comprising carboxymethylcellulose and otherderivatives of cellulose and natural gums, as well as the Carbopols, ofreduced solubility due to cross-linkages. Also excluded are the zinc,magnesium and similar metal complexes of these polymericpolycarboxylates.

Other operative polymeric polycarboxylates include those disclosed inU.S. Pat. No. 3,956,180 referred to above, such as the 1:1 copolymers ofmaleic anhydride with ethyl acrylate, hydroxyethyl methacrylate,N-vinyl-2-pyrrollidone, or ethylene, the latter being available forexample as Monsanto EMA No. 1103, M.W. 10,000, and EMA Grade 61, and 1:1copolymers of acrylic acid with methyl or hydroxyethyl methacrylate,methyl or ethyl acrylate, isobutyl vinyl ether or N-vinyl-2-pyrrolidone.

Additional operative polymeric polycarboxylates disclosed in abovereferred to U.S. Pat. Nos. 4,138,477 and 4,183,914, include copolymersof maleic anhydride with styrene, isobutylene or ethyl vinyl ether,polyacrylic, polyitaconic and polymaleic acids, and sulfoacrylicoligomers of M.W. as low as 1,000, available as Uniroyal ND-2.

Suitable generally are polymerized olefinically or ethylenicallyunsaturated carboxylic acids containing an activated carbon-to-carbonolefinic double bond and at least one carboxyl group, that is, an acidcontaining an olefinic double bond which readily functions inpolymerization because of its presence in the monomer molecule either inthe alpha-beta position with respect to a carboxyl group or as part of aterminal methylene grouping. Illustrative of such acids are acrylic,methacrylic, ethacrylic, alpha-chloroacrylic, crotonic, beta-acryloxypropionic, sorbic, alpha-chlorsorbic, cinnamic, beta-styrilacrylic,muconic, itaconic, citraconic, mesaconic, glutaconic, aconitic,alpha-phenylacrylic, 2-benzyl acrylic, 2-cyclohexylacrylic, angelic,umbellic, fumaric, maleic acids and anhydrides. Other different olefinicmonomers copolymerizable with such carboxylic monomers includevinylacetate, vinyl chloride, dimethyl maleate and the like. Copolymerscontain sufficient carboxylic salt groups for water-solubility.

The synthetic anionic linear polymeric polycarboxylate component ismainly a hydrocarbon with optional halogen and O-containing substituentsand linkages as present in for example ester, ether and OH groups, andis generally employed in the instant compositions in approximate weightamounts of 0.05 to 3%, preferably 0.05 to 2%, more preferably 0.1 to 2%.Amounts in the upper portions of these ranges are typically employed indentifrice compositions, meaning oral compositions generally containinga dental abrasive and used in conjunction with brushing of the teeth,e.g. tooth pastes, gels, creams and powders. Amounts in excess of theseranges may be employed for thickening or gelling purposes.

The source of fluoride ions, or fluorine-providing compounds, requiredaccording to this invention as an essential component of the describedinhibitor combination, are well known in the art as anti-caries agentsand also act as such agents in the practice of this invention. Thesecompounds may be slightly soluble in water or may be fullywater-soluble. They are characterized by their ability to releasefluoride ions in water and by freedom from undesired reaction with othercompounds of the oral preparation. Among these materials are inorganicfluoride salts, such as soluble alkali metal, alkaline earth metalsalts, for example, sodium fluoride, potassium fluoride, ammoniumfluoride, calcium fluoride, a copper fluoride such as cuprous fluoride,zinc fluoride, barium fluoride, sodium fluorsilicate, ammoniumfluorosilicate, sodium fluorozirconate, sodium monofluoro-phosphate,aluminum mono- and di-fluorophosphate, and fluorinated sodium calciumpyrophosphate. Alkali metal and tin fluorides, such as sodium andstannous fluorides, sodium monofluorophosphate (MFP) and mixturesthereof, are preferred.

The amount of fluorine-providing compound is dependent to some extentupon the type of compound, its solubility, and the type of oralpreparation, but it must be a nontoxic amount, generally about 0.005 toabout 3.0% in the preparation. In a dentifrice preparation, e.g. gel,cream, toothpaste or toothpowder, an amount of such compound whichreleases up to about 2,000 ppm of F ion by weight of the preparation isconsidered satisfactory. Any suitable minimum amount of such compoundmay be used, but it is preferable to employ sufficient compound torelease about 300 to about 2,000 ppm, more preferably about 800 to about1,500 ppm of fluoride ion. Typically, in the cases of alkali metalfluorides and stannous fluoride, this component is present in an amountup to about 2% by weight, based on the weight of the preparation, andpreferably in the range of about 0.05% to 1%. In the case of sodiummonofluorophosphate, the compound may be present in an amount of about0.1-3%, more typically about 0.76%.

In oral preparations such as mouthwashes, lozenges and chewing gum, thefluorine-providing compound is typically present in an amount sufficientto release up to about 500 ppm, preferably about 25 to about 300 ppm byweight of fluoride ion. Generally about 0.005 to about 1.0 wt.% of suchcompound is present.

In certain highly preferred forms of the invention the oral compositionmay be substantially liquid in character, such as a mouthwash or rinse.In such a preparation the vehicle is typically a water-alcohol mixturedesirably including a humectant as described below. Generally, theweight ratio of water to alcohol is in the range of from about 1:1 toabout 20:1, preferably about 3:1 to 10:1 and more preferably about 4:1to about 6:1. The total amount of water-alcohol mixture in this type ofpreparation is typically in the range of from about 70% to about 99.9%by weight of the preparation.

The pH of such liquid and other preparations of the invention isgenerally in the range of from about 4.5 to about 9 and typically fromabout 5.5 to 8. The pH is preferably in the range of from about 6 toabout 8.0. It is noteworthy that the compositions of the invention maybe applied orally at a pH below 5 without substantially decalcifying orotherwise damaging dental enamel. The pH can be controlled with acid(e.g. citric acid or benzoic acid) or base (e.g. sodium hydroxide) orbuffered (as with sodium citrate, benzoate, carbonate, or bicarbonate,disodium hydrogen phosphate, sodium dihydrogen phosphate, etc.).

In certain other desirable forms of this invention, the oral compositionmay be substantially solid or pasty in character, such as toothpowder, adental tablet, a toothpaste, gel or dental cream. The vehicle of suchsolid or pasty oral preparations generally contains polishing material.Examples of polishing materials are water-insoluble sodiummetaphosphate, potassium metaphosphate, tricalcium phosphate, dihydratedcalcium phosphate, anhydrous dicalcium phosphate, calcium pyrophosphate,magnesium orthophosphate, trimagnesium phosphate, calcium carbonate,aluminum silicate, zirconium silicate, silica, bentonite, and mixturesthereof. Other suitable polishing materials include the particulatethermosetting resins described in U.S. Pat. No. 3,070,510 of Dec. 15,1962 such as melamine-, phenolic-, and urea-formaldehydes, andcross-linked polyepoxides and polyesters. Preferred polishing materialsinclude crystalline silica having particle sizes of up to about 5microns, a mean particle size of up to about 1.1 microns, and a surfacearea of up to about 50,000 cm.² /gm., silica gel or colloidal silica,and complex amorphous alkali metal aluminosilicate.

When visually clear gels are employed, a polishing agent of colloidalsilica, such as those sold under the trademark SYLOID as Syloid 72 andSyloid 74 or under the trademark SANTOCEL as Santocel 100 and alkalimetal alumino-silicate complexes are particularly useful, since theyhave refractive indices close to the refractive indices of gellingagent-liquid (including water and/or humectant) systems commonly used indentifrices.

Many of the so-called "water-insoluble" polishing materials are anionicin character and also include small amounts of soluble material. Thus,insoluble sodium metaphosphate may be formed in any suitable manner asillustrated by Thorpe's Dictionary of Applied Chemistry, Volume 9, 4thEdition, pp. 510-511. The forms of insoluble sodium metaphosphate knownas Madrell's salt and Kurrol's salt are further examples of suitablematerials. These metaphosphate salts exhibit only a minute solubility inwater, and therefore are commonly referred to as insolublemetaphosphates (IMP). There is present therein a minor amount of solublephosphate material as impurities, usually a few percent such as up to 4%by weight. The amount of soluble phosphate material, which is believedto include a soluble sodium trimetaphosphate in the case of insolublemetaphosphate, may be reduced or eliminated by washing with water ifdesired. The insoluble alkali metal metaphosphate is typically employedin powder form of a particle size such that no more than about 1% of thematerial is larger than about 37 microns.

The polishing material is generally present in the solid or pastycompositions in weight concentrations of about 10% to about 99%.Preferably, it is present in amounts ranging from about 10% to about 75%in toothpaste, and from about 70% to about 99% in toothpowder.

In a toothpaste, the liquid vehicle may comprise water and humectanttypically in an amount ranging from about 10% to about 90% by weight ofthe preparation. Glycerine, propylene glycol, sorbitol, polypropyleneglycol and/or polyethylene glycol (e.g. 400-600) exemplify suitablehumectants/carriers. Also advantageous are liquid mixtures of water,glycerine and sorbitol. In clear gels where the refractive index is animportant consideration, about 3-30 wt.% of water, 0 to about 80 wt.% ofglycerine, and about 20-80 wt.% of sorbitol is preferably employed.

Toothpastes, creams and gels typically contain a natural or syntheticthickener or gelling agent in proportions of about 0.1 to about 10,preferably about 0.5 to about 5, wt.%. A suitable thickener is synthetichectorite, a synthetic colloidal magnesium alkali metal silicate complexclay available for example as Laponite (e.g. CP, SP 2002, D) marketed byLaporte Industries Limited. Laponite D analysis shows, approximately byweight, 58.00% SiO₂, 25.40% MgO, 3.05% Na₂ O, 0.98% Li₂ O, and somewater and trace metals. Its true specific gravity is 2.53 and it has anapparent bulk density (g./ml. at 8% moisture) of 1.0.

Other suitable thickeners include Irish moss, gum tragacanth, starch,polyvinylpyrrolidone, hydroxyethypropylcellulose, hydroxybutyl methylcellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose (e.g.available as Natrosol), sodium carboxymethyl cellulose, and colloidalsilica such as finely ground Syloid (e.g. 244).

It will be understood that, as is conventional, the oral preparationsare to be sold or otherwise distributed in suitable labelled packages.Thus a jar of mouthrinse will have a label describing it, in substance,as a mouthrinse or mouthwash and having directions for its use; and atoothpaste, cream or gel will usually be in a collapsible tube,typically aluminum, lined lead or plastic, or other squeeze, pump orpressurized dispenser for metering out the contents, having a labeldescribing it, in substance, as a toothpaste, gel or dental cream.

Organic surface-active agents are used in the compositions of thepresent invention to achieve increased prophylactic action, assist inachieving thorough and complete dispersion of the anticalculus agentthroughout the oral cavity, and render the instant compositions morecosmetically acceptable. The organic surface-active material ispreferably anionic, nonionic or ampholytic in nature, and it ispreferred to employ as the surface-active agent a detersive materialwhich imparts to the composition detersive and foaming properties.Suitable examples of anionic surfactants are water-soluble salts ofhigher fatty acid monoglyceride monosulfates, such as the sodium salt ofthe monosulfated monoglyceride of hydrogenated coconut oil fatty acids,higher alkyl sulfates such as sodium lauryl sulfate, alkyl arylsulfonates such as sodium dodecyl benzene sulfonate, higher alkylsulfoacetates, higher fatty acid esters of 1,2 dihydroxy propanesulfonate, and the substantially saturated higher aliphatic acyl amidesof lower aliphatic amino carboxylic acid compounds, such as those having12 to 16 carbons in the fatty acid, alkyl or acyl radicals, and thelike. Examples of the last mentioned amides are N-lauroyl sarcosine, andthe sodium, potassium, and ethanolamine salts of N-lauroyl, N-myristoyl,or N-palmitoyl sarcosine which should be substantially free from soap orsimilar higher fatty acid material. The use of these sarcosinatecompounds in the oral compositions of the present invention isparticularly advantageous since these materials exhibit a prolonged andmarked effect in the inhibition of acid formation in the oral cavity dueto carbohydrate breakdown in addition to exerting some reduction in thesolubility of tooth enamel in acid solutions. Examples of water-solublenonionic surfactants are condensation products of ethylene oxide withvarious reactive hydrogen-containing compounds reactive therewith havinglong hydrophobic chains (e.g. aliphatic chains of about 12 to 20 carbonatoms), which condensation products ("ethoxamers") contain hydrophilicpolyoxyethylene moieties, such as condensation products of poly(ethyleneoxide) with fatty acids, fatty alcohols, fatty amides, polyhydricalcohols (e.g. sorbitan monostearate) and polypropyleneoxide (e.g.Pluronic materials).

Various other materials may be incorporated in the oral preparations ofthis invention such as whitening agents, preservatives, silicones,chlorophyll compounds, other anticalculus agents, and/or ammoniatedmaterial such as urea, diammonium phosphate, and mixtures thereof. Theseadjuvants, where present, are incorporated in the preparations inamounts which do not substantially adversely affect the properties andcharacteristics desired. Significant amounts of zinc, magnesium andother metal salts and materials, generally soluble, which would complexwith the active components of the instant invention are to be avoided.

Any suitable flavoring or sweetening material may also be employed.Examples of suitable flavoring constituents are flavoring oils, e.g. oilof spearmint, peppermint, wintergreen, sassafras, clove, sage,eucalyptus, marjoram, cinnamon, lemon, and orange, and methylsalicylate. Suitable sweetening agents include sucrose, lactose,maltose, sorbitol, xylitol, sodium cyclamate, perillartine, APM(aspartyl phenyl alanine, methyl ester), saccharine and the like.Suitably, flavor and sweetening agents may together comprise from about0.1% to 5% more of the preparation.

In the preferred practice of this invention an oral compositionaccording to this invention such as a mouthwash or dentifrice containingthe described polyphosphate and inhibitor combination in an amounteffective to inhibit calculus on dental surfaces is preferably appliedregularly to dental enamel, such as every second or third day orpreferably from 1 to 3 times daily, at a pH of about 4.5 to about 9,generally about 5.5 to about 8, preferably about 6 to 8, for at least 2weeks up to 8 weeks or more up to lifetime.

The compositions of this invention can be incorporated in lozenges, orin chewing gum or other products, e.g. by stirring into a warm gum baseor coating the outer surface of a gum base, illustrative of which may bementioned jelutone, rubber latex, vinylite resins, etc., desirably withconventional plasticizers or softeners, sugar or other sweeteners orcarbohydrates such as glucose, sorbitol and the like.

The following examples are further illustrative of the nature of thepresent invention, but it is understood that the invention is notlimited thereto. All amounts and proportions referred to herein and inthe appended claims are by weight and temperatures are in degrees C.unless otherwise indicated.

EXAMPLE A Effect of Salivary Enzymes on Inhibition of HAP Formation byHMP* and TSPP**

The in vitro formation of HAP is measured titrimetrically via a pH statprocedure. Stock solutions of 0.1M CaCl₂ and 0.1M NaH₂ PO₄ are preparedfresh in carbonate-free deionized distilled water. To 23 ml CO₂ -freedeionized distilled water 1.0 ml. of the stock phosphate solution and1.0 ml. of an aqueous solution of 1×10⁻⁴ M of the anticalculus agentbeing tested are added followed by 1.0 ml. of the stock calcium chloridesolution which initiates the reaction. The reaction is conducted at pH7.4 under a nitrogen atmosphere. Consumption of 0.1N NaOH is recordedautomatically from which the time required for crystal formation isdetermined. Table A shows the results of this procedure.

                  TABLE A                                                         ______________________________________                                        Time of Crystal Growth Inhibition (Hrs.)                                      Anticalculus                        Alk.                                      Agent    Water   Saliva  Pyrophosphatase                                                                          Phosphatase                               ______________________________________                                        HMP*     >12     >3      1.0        2.0                                       TSPP**   0.8     0.4     0.3        0.0                                       ______________________________________                                         *Sodium hexametaphosphate                                                     **Tetrasodium pyrophosphate                                              

Table A shows that in water both agents significantly delay HAPformation. However, the effectiveness of these agents is drasticallyreduced when incubated with saliva as evidenced by the shorter delaytime. This reduction in efficacy is due to the enzymatic hydrolysis ofP-O-P bonds. Incubation of these agents with pyrophosphatase andalkaline phosphatase drastically reduces the delay period and indicatesthe susceptibility of the P-O-P bond to hydrolysis by phosphatases.

EXAMPLE 1 Stabilization of TSPP, STPP* and HMP to Enzymatic Hydrolysisin Presence of Inhibitors

Enzymatic hydrolysis is conducted in 100 millimolar morpholinopropanesulfonic acid-NaOH buffer solution (pH 7.0) containing 1.3 mg./ml. ofthe respective polyphosphate. Inhibitors of this invention are added(except to the control) to a final concentration of 1,000 ppm fluorideion (from NaF) and 0.5% of the sodium salt of hydrolyzedmethoxyethylene-maleic anhydride (1:1) copolymer, M.W. 70,000 (GantrezS-97 Pharmaceutical Grade). Equal activities of acid, alkaline andinorganic pyrophosphatase are then added to yield a total phosphataseactivity of 0.3 units/ml. Samples of each test solution are taken andtotal orthophosphate available in each sample measured after 3 hourshydrolysis in 4N HCl at 100° C. The reaction mixtures are incubated at37° C. with shaking and aliquots taken at appropriate times through atleast 90 minutes for orthophosphate determination. Table 1 shows theresults expressed as percent orthophosphate released due to hydrolysisof the polyphosphate.

                  TABLE 1                                                         ______________________________________                                               Percent Orthophosphate                                                        Released in 90 min.                                                    Anticalculus        With      Percent Relative                                Agent    Control    Inhibitors                                                                              Protection                                      ______________________________________                                        TSPP*    98         58        41                                              STPP*    100        62        39                                              HMP      95         40        57                                              ______________________________________                                         *Sodium tripolyphosphate                                                 

Table I shows that after 90 min. incubation in the presence of enzymegreater than 95% of the available orthophosphate is released from thepolyphosphates in the absence of the inhibitors. With inhibitors,hydrolysis of P-O-P bonds in pyrophosphate, tripolyphosphate, andhexametaphosphate is reduced by 41%, 39% and 57%, respectively. Itshould be noted that the enzyme activities used in this study are atleast 2-3 fold greater than those normally found in saliva. These dataindicate that the combination of inhibitors of this inventionsignificantly reduces enzymatic hydrolysis of the linear polyphosphates.

EXAMPLE 2 Dentifrice Composition

                  TABLE 2                                                         ______________________________________                                        A.    Ingredient            Parts                                             ______________________________________                                        Deionized water         37.578                                                Glycerine               25.000                                                Zeo 49B (Silicon Dioxide)                                                                             21.500                                                HMP (Hexaphos)          6.000                                                 Syloid 244 (synthetic silica)                                                                         3.000                                                 Sodium Lauryl Sulfate   1.200                                                 Flavor                  1.000                                                 Gantrez (S-97 Pharmaceutical Grade)                                                                   1.000                                                 Sodium Hydroxide (50% Solution)                                                                       1.000                                                 Xanthan Gum             1.000                                                 Sodium Benzoate         0.500                                                 Titanium Dioxide        0.500                                                 Sodium Saccharin        0.300                                                 Sodium Fluoride         0.242                                                 ______________________________________                                    

B. Formulation of A above but containing TSPP instead of HMP.

C. Formulation of A above but containing 5 parts of STPP instead of 6parts of HMP.

EXAMPLE 3 Mouthwash

    ______________________________________                                                         Parts                                                        ______________________________________                                        TSPP               3.0                                                        Ethyl Alcohol      15.0                                                       Gantrez S-97       0.05                                                       Glycerol           10.0                                                       Flavor             0.4                                                        Sodium saccharin   0.03                                                       NaF                0.05                                                       Pluronic F 108*    2.0                                                        Deionized Water to Q.S.                                                                          100                                                        ______________________________________                                         *Polyoxyethylenated polyoxypropylene nonionic block polymer surfactant.  

EXAMPLE 4 Lozenges

    ______________________________________                                                       Parts                                                          ______________________________________                                        Sugar            75-98                                                        Cornsyrup         1-20                                                        Flavor oil       0.1-1.0                                                      Tablet lubricant 0.1-5                                                        Polyphosphate    0.1-5                                                        Gantrez polymer  0.05-3                                                       NaF              0.01-0.05                                                    Water            0.01-0.2                                                     ______________________________________                                    

EXAMPLE 5 Chewing Gum

    ______________________________________                                                        Parts                                                         ______________________________________                                        Gum base          10 to 50                                                    Binder             3 to 10                                                    Filler             5 to 80                                                    (sorbitol, mannitol or                                                        combination thereof)                                                          Artificial sweetener                                                                            0.1 to 5                                                    Polyphosphate     0.1 to 5                                                    Gantrez polymer   0.1 to 1.0                                                  NaF               0.01-0.05                                                   Flavor            0.1 to 5                                                    ______________________________________                                    

This invention has been described with respect to certain preferredembodiments and it will be understood that modifications and variationsthereof obvious to those skilled in the art are to be included withinthe purview of this application and the scope of the appended claims.

We claim:
 1. A method of inhibiting dental calculus comprising applyingto teeth a calculus-inhibiting amount of a dentifrice composition havinga pH of about 4.5 to about 9 containing, in an orally acceptablevehicle, approximately by weight, 0.1 to 7% of one or a mixture oflinear molecularly dehydrated polyphosphate salts selected from thegroup consisting of water soluble alkali metal pyrophosphates,tripolyphosphates and hexametaphosphates, a dentally acceptable silicapolishing material, and for the purpose of inhibiting hydrolysis ofP-O-P bonds in said polyphosphate salts by phosphatase enzymes in salivato orthophosphates which are relatively ineffective as inhibitors ofhydroxyapatite formation, an amount of a fluorine ion source sufficientto supply 25 ppm. to 2,000 ppm. of fluoride ions and 0.05% to 3% of awater-soluble alkali metal or ammonium synthetic anionic linearpolymeric polycarboxylate salt having a molecular weight of about 1,000to about 1,000,000 said composition when so applied to teeth beingeffective to inhibit dental calculus.
 2. A method effective forinhibiting dental calculus comprising applying to teeth acalculus-inhibiting amount of a toothpaste, gel or cream formulationmade with, approximately by weight:(a) 2-6% of water soluble tetraalkalimetal pyrophosphate, (b) an amount of a fluoride ion source sufficientto supply 300 ppm. to 2,000 ppm of fluoride ions, (c) 0.1 to 2% of awater soluble alkali metal or ammonium salt of a copolymer of vinylmethyl ether and maleic acid or anhydride having a molecular weight ofabout 30,000 to about 500,000, and (d) an orally acceptable vehiclecontaining water, humectant and about 10 to 75% of silica dentalpolishing material, said formulation when so applied to teeth beingeffective for inhibiting dental calculus.
 3. A method effective forinhibiting dental calculus comprising brushing teeth with acalculus-inhibiting amount of a toothpaste, gel or cream formulationmade with, approximately by weight:(a) 6% of water soluble tetraalkalimetal pyrophosphate, (b) an amount of a fluoride ion source sufficientto supply 800 ppm to 1,500 ppm. of fluoride ions, (c) 1% of a sodiumsalt of a hydrolyzed copolymer of vinyl methyl ether and maleic acid oranhydride having a molecular weight of about 70,000, and (d) an orallyacceptable vehicle containing water, humectant and about 10 to 75% ofsilica dental polishing material, said formulation when so used forbrushing teeth being effective for inhibiting dental calcus.
 4. A methodaccording to claim 1 wherein said fluoride ion source comprises sodiumfluoride.
 5. A method according to claim 4 wherein said linear polymericpolycarboxylate comprises a copolymer of vinyl methyl ether and maleicacid or anhydride.
 6. A method according to claim 5 wherein saidcopolymer has a molecular weight of about 30,000 to about 500,000.
 7. Amethod according to claim 5 wherein said polyphosphate salt comprises asodium pyrophosphate.
 8. A method according to claim 1 wherein saidcomposition comprises at least one member of the group consisting ofdialkalimetal diacid pyrophosphate, trialkali metal monoacidpyrophosphate and tetraalkali metal pyrophosphate.
 9. A method accordingto claim 8 wherein said alkali metal in said pyrophosphates isindependently sodium or potassium.
 10. A method as defined in claim 6wherein said composition contains about 2 to about 6% of one or amixture of water soluble alkali metal pyrophosphates and about 0.1 toabout 2% of said copolymer.
 11. A method as defined in claim 10 whereinsaid copolymer has a molecular weight of about 70,000.